The objectives of this research project are to elucidate some of the mechanisms involved in the release of transmitter from the motor nerve terminal and to define the mechanism of transmitter storage and mobilization in the nerve terminal. It is hoped that this project will lead to a better understanding of neuromuscular transmission and possibly a means of controlling the processes involved. Intracellular recording techniques will be used to examine the basis for depression in transmitter release following repetitive stimulation and a subsequent potentiation period. The role of sodium ions, microtubules, and glutathione in the release mechanism will be investigated. The store of transmitter immediately available for release during maintained stimulation is dependent on replenishment by mobilization from a mobilization store and synthesis of new transmitter. An electrophysiological method will be used to measure the rate of transmitter synthesis. The role of microtubules in the mobilization process will be examined. The proposed study of these events should prove useful in interpreting the complex mechanisms involved in neuromuscular and synaptic transmission. This may lead to a better understanding and possibly a means of controlling certain neuromuscular diseases such as myasthenia gravis.